So far, 7-ethyl-10-hydroxycamptothecin is usually prepared in two reaction steps. In the first reaction step, 7-ethylcamptothecin of formula II
is oxidized with hydrogen peroxide in acetic acid under formation of 7-ethylcamptothecin 1-oxide of formula III
which in the second reaction step is dissolved-in the solvent system dioxane-acetonitrile-water and the solution is irradiated with UV light in the presence of sulfuric acid to afford the desired 7-ethyl-10-hydroxycamptothecin (see U.S. Pat. No. 4,473,692 and U.S. Pat. No. 4,513,138 and Zhongguo Yaowu Huaxue Zazhi 2001, 11 (4), 238-240).
However, this method of manufacturing of 7-ethyl-10-hydroxycamptothecin suffers from the fact that the oxidation of 7-ethylcamptothecin in the first reaction step requires relatively great amount of acetic acid (300 ml of acetic acid per 1 gram of 7-ethylcamptothecin). In the isolation of the obtained 7-ethylcamptothecin 1-oxide it is necessary to evaporate one fourth of the acetic acid volume, add water to the evaporation residue and subsequently collect the precipitated 7-ethylcamptothecin 1-oxide by filtration. This isolation procedure is demanding and affects very unfavourably the yield of 7-ethylcamptothecin 1-oxide. In the second step, the isolation of 7-ethyl-10-hydroxycamptothecin, consists in removal of the solvent mixture by distillation, dilution with water, extraction with chloroform and drying the chloroform layer over magnesium sulfate, followed by purification on a silica gel column with the aim to remove impurities arising in the UV irradiation. In spite of this complicated isolation procedure, the obtained 7-ethyl-10-hydroxycamptothecin still contains up to 22% by weight of 7-ethylcamptothecin. In this method the total yield of both reaction steps is only about 38%.
The aim of the invention is to find a less demanding method of producing 7-ethyl-10-hydroxycamptothecin that would afford 7-ethyl-10-hydroxycamptothecin in higher yields and higher purity. This aim has been achieved by the method according to the present invention.